Oral hygiene compositions and polymers active therein

ABSTRACT

Oral hygiene compositions effective for preventing the adherent deposition of cariogenic bacteria on teeth comprise as active constituents polymers having defined repeating units comprising hydrocarbyl groups with pendant carboxyl and pendant polyalkylene oxide groups in defined ratio. The polymers themselves, their preparation and a process for treating teeth with the compositions are also claimed.

This is a division of application Ser. No. 07/016,257, filed Feb. 19,1987 now abandoned, which, in turn, is a division of Ser No. 06/793,763,filed 11/1/85, now abandoned.

This invention relates to oral hygiene compositions, to polymers activetherein and to methods of using such compositions to prevent or inhibitattachment of bacteria to teeth.

The prevention of the adherent deposition of dental plaque on mammalian(particularly human) teeth is a highly desired result. Dental plaqueresults when cariogenic and other types of bacteria aggregate incolonies on the surface of teeth and form a deposit thereon whichadheres tenaciously to the surface. It is believed that the formation ofplaque on the surface of a tooth is one of the first steps in thedevelopment of dental caries and periodontal disease.

Many attempts have been made to prevent the deposition of plaque ontooth surfaces and to effect removal of plaque from such surfaces. Forexample, fluoride, brushing and dental flossing treatments have beentried. Such treatments are typically directed to counteracting thesecondary effects of plaque on the teeth and gums, or to the removal ofplaque that is formed on and adhering to the teeth and surroundingtissue. Such treatments are not, however, entirely successful and mustbe supplemented with periodic treatment by dental professionals.

Recently it has been proposed that the use of oral compositions whichcontain certain polymers may be useful in preventing deposition ofdental plaque. For example, for such use, certain sulphonated vinylaromatic polymers are suggested in U.S. Pat. No. 4,375,461; the productsof the reaction of long chain aliphatic alkylene amine andtrimetaphosphoric acid are suggested in U.S. Pat. No. 4,234,568; certainbis-[4-(alkylamino)-1-Pyridinium]alkanes and trimetaphosphoric acid aresuggested in U.S. Pat. No. 4,234,568; certainbis-[4-(alkylamino)-1-pyridinium]alkanes are suggested in U.S. Pat. No.4,206,215; certain sulphonated polyamino acids are suggested in U.S.Pat. No. 4,314,991; and copolymers of glutamic acid and tyrosine aresuggested in U.S. Pat. No. 4,339,431.

It has also been claimed in U.S. Pat. No. 3,542,917 that the formationof dental calculus, which is a hard calcified deposit that accumulateson or near tooth surfaces, may be inhibited by treatment of the teethwith a composition containing a polyester of a polycarboxylic acidhaving 3 to 6 carboxyl groups with a polyalkylene ether having 2 to 4hydroxyl groups and a molecular weight of 400 to 10,000. In ourexperience, however, compositions falling within the scope of the claimsof U.S. Pat. No. 3,542,917 are not very effective in preventing theadherent deposition of cariogenic bacteria, or the plaque resultingtherefrom, on tooth surfaces.

We have now found that certain pharmaceutical compositions (ashereinafter defined) containing certain polymers (also as hereinafterdefined) are highly effective for preventing or significantly reducingthe adherent deposition of cariogenic and other micro-organisms commonlyfound in an oral environment, and also dental plaque resultingtherefrom, on tooth surfaces or simulated tooth surfaces (made ofhydroxyapatite as are mammalian tooth surfaces) when the surfaces aretreated therewith.

According to the present invention there is provided an oral hygienecomposition comprising an effective amount of at least one polymer whichpolymer comprises one or more repeating units of general structure A##STR1## and one or more repeating units of general structure B ##STR2##wherein X, which in the repeating units of structure A may be the sameor different, and Y, which in the repeating units of structure B may bethe same or different, are optionally substituted hydrocarbyl residuesproviding a backbone for the polymer;

R¹, which in the same repeating unit of structure B (when n or q is 2 ormore) or in different repeating units of structure B may be the same ordifferent, is hydrogen or methyl;

R², which in the same repeating unit of structure B (when n or q is 2 ormore) or in different repeating units of structure B may be the same ordifferent, is hydrogen or methyl;

except that R¹ and R² in a single unit (CHR¹ CHR² O) cannot both bemethyl;

R³, which in the same repeating unit of structure B (when q is 2 ormore) or in different repeating units of structure B may be the same ordifferent, is hydrogen, or a lower alkyl group containing up to fivecarbon atoms, or an acyl group derived from an alkanoic acid having upto five carbon atoms;

n is a number of from 1 to 60;

p is a number of from 1 to 4, and q is a number of from 1 to 4;

and wherein each (CO₂ H) group is joined via an intermediary orintermediaries L to the hydrocarbyl residue X, and in cases where p is 2to 4 may be joined by L to the same or different carbon atoms of X; andwherein L represents one or more intermediaries, and wherein L may bethe same or different in the repeat units of structure A and is selectedfrom one or more direct links and one or more groups of atoms each groupproviding a chain of one or more atoms for linking a (CO₂ H) group withX, except that more than two (CO₂ H) groups cannot be directly linked tothe same carbon atoms in X;

and wherein each (CHR¹ CHR² O)n group is joined via an intermediary orintermediaries M to the hydrocarbyl residue Y, and in cases where q is 2to 4 may be joined by M to the same or different carbon atoms of Y; andwherein M represents one or more intermediaries, and wherein M may bethe same or different in the repeat units of structure B and is selectedfrom one or more direct links and one or more groups of atoms each groupproviding a chain of one or more atoms for linking a (CHR¹ CHR₂ O)_(n)group with Y, except that more than two (CHR¹ CHR₂ O)_(n) groups cannotbe directly linked to the same carbon atom in Y;

and wherein the ratio of the number of --CO₂ H groups to the number of--CHR¹ CHR₂ O-- groups is within the range of from 1:20 to 20:1;

and said composition also comprising a pharmaceutically acceptablevehicle for said polymer.

It is to be understood that the definition of the polymer contained inthe composition (as given above) is also intended to embrace a polymerin which at least some of the carboxyl groups in the repeat units ofstructure A have been converted to the corresponding salt anions CO₂ ⁻(these being considered as --CO₂ H groups as far as the ratio ofcarboxyl to --CHR¹ CHR₂ O-- groups is concerned), the correspondingcations for example being those of (preferably) alkali metals (e.g. Na⁺,K⁺), or alkaline earth metals, or ammonium (NH₄ ⁺) Such a conversioncould be effected as a result of incorporating the polymer into analkaline pharmaceutically acceptable vehicle, or could be effected bytreatment with a suitable alkaline material before incorporation into apharmaceutical vehicle.

As far as we are aware, polymers falling within the definition as setout above are themselves new and inventive materials.

According there is further provided according to the invention whichcomprises one or more repeating units of structure A ##STR3## and one ormore repeating units of structure B ##STR4## wherein X, Y, R¹, R², R³,n, p, q, L, and M, and the ratio of the number of --CO₂ H groups to--CHR¹ CHR² O-- groups, are as defined hereinbefore.

In structure A, each carboxyl group is joined to the hydrocarbyl residueX by means of an intermediary or intermediaries (i.e. by a linkingentity or entities), this or these being denoted by L, which is selectedfrom one or more direct links (i.e. one or more direct bonds) and one ormore groups of atoms each group providing a chain of one or more atomsfor linking a carboxyl group(s) with X. In cases where p is 2 to 4, eachcarboxyl group may be joined by L to the same or, in cases where Lrepresents more than one intermediary, to the same or different carbonatoms in X, although more than 2 carboxyl groups cannot of course bedirectly linked to the same carbon atom of X (and also assuming that insuch cases X has at least 2 carbon atoms, whereas it should beappreciated that it is within the scope of the invention for X to haveonly 1 carbon atom). It will be noted that in principle L can representup to 4 separate intermediaries in structure A (in cases where p is 4).L may be the same or different in the repeat units of structure A.

In cases where L represents one or more groups of atoms each groupproviding a linking chain of atoms, the chain will normally comprise oneor more carbon atoms (which could e.g. include carbon atoms in an arylring) and/or hetero atoms (particularly N and/or O). Examples ofpossible linkages provided by L are: ##STR5## where (apart from thedirect link) the top link is to X and the bottom link(s) is to carboxyl.It is preferred in the present invention, however, that L is one or moredirect links, so that each carboxyl group is joined directly to a carbonatom of X in the polymer backbone.

It is preferred in structure A that p is 1 or 2 (so that L can thenrepresent one, or at most, two intermediaries).

In structure B, each (CHR¹ CHR² O)_(n) group is joined to thehydrocarbyl residue Y by means of an intermediary or intermediaries(i.e. by a linking entity or entities), this or these being denoted byM, which is selected from one or more direct links (i.e. one or moredirect bonds) and one or more groups of atoms each group providing achain of one or more atoms for linking a (CHR¹ CHR₂ O)_(n) group(s) withY. In cases where q is 2 to 4, each (CHR¹ CHR₂ O)_(n) group may bejoined by M to the same or, in cases where M represents more than oneintermediary, to the same or different carbon atoms in Y, although morethan two (CHR¹ CHR₂ O)_(n) groups cannot of course be directly linked tothe same carbon atom of Y (and also assuming that in such cases Y has atleast 2 carbon atoms, whereas it should be appreciated that it is withinthe scope of the invention for Y to have only 1 carbon atom). It will benoted that in principle M can represent up to 4 separate intermediariesin structure B (in cases where q is 4). M may be the same or differentin the repeat units of structure B.

While M may represent one or more direct links, it is preferred in thepresent invention that M is one or more groups of atoms each groupproviding a linking chain of atoms; such a chain will normally compriseone or more carbon atoms (which could e.g. include carbon atoms in anaryl ring) and/or hetero atoms (particularly N and/or O). Particularlypreferred examples of linkages provided by M are: ##STR6## where the toplink is to Y and the bottom link is to (CHR¹ CHR² O)_(n).

It is preferred in structure B that q is 1 or 2 (so that M can thenrepresent one, or at most two intermediaries).

Preferably the structure A represents the repeat unit derived from thepolymerization (usually free-radical initiated) of a polymerisableolefinically unsaturated carboxylic acid. Examples of such acids areacrylic acid, methacrylic acid, maleic (or fumaric) acid, itaconic acidand the acids of formulae ##STR7## respectively giving rise to thefollowing structures for A: ##STR8##

Particularly preferred acids at our present stage of development aremethacrylic, acrylic and maleic acid. Normally the repeat units A willall be of the same specific structure, although the scope of theinvention is intended to embrace polymers having repeat units A of morethan one specific structure (e.g. 2 or different specific structures).

Preferably the structure B represents the repeat unit derived from thepolymerization (usually free-radical initiated) of a polymerisableolefinically unsaturated ester or amide formed from the reaction of anunsaturated carboxylic acid (or an esterifiable or amidifiablederivative thereof such as an acid chloride or anhydride) and a hydroxycompound of formula HO--CHR¹ CHR² O)_(n) R³ (to form the ester) or anamine of formula H₂ N--CHR¹ CHR² O)_(n) R³ (to form the amide).Preferably the acid used is acrylic or methacrylic acid, particularlythe latter, giving rise, respectively, to the following structures forB: ##STR9##

Normally the repeat units B will all be of the same specific structure,although the scope of the invention is intended to embrace polymershaving repeat units B of more than one specific structure (e.g. 2 or 3different specific structures).

The repeating units of structure B may alternatively be formed by thepartial esterification or amidification of an already-polymerisedolefinically unsaturated carboxylic acid (or an esterifiable oramidifiable derivative thereof such as an acid chloride or anhydride)using, preferably, an alcohol of formula HO--CHR¹ CHR² O)_(n) R³ or anamine of formula H₂ N--CHR¹ CHR² O)_(n) R³. The remaining (unesterifiedor unamidified) carboxyl groups with their associated sections of thepolymer backbone will of course provide units of structure A (it may ofcourse be necessary to hydrolyse residual acid-derivative groups back tocarboxyl when an acid derivative is used).

In one interesting aspect of this alternative method for producing unitsof structures A and B, an olefinically unsaturated cyclic anhydride maybe used to produce both the acid and ester/amide groups of the resultingpolymer. For example, maleic anhydride may be polymerised to form apolymer of repeat unit ##STR10## and the resulting repeating units A andB after esterification with HO--(CHR¹ CHR² O)_(n) R³ or amidificationwith H₂ N--(CHR¹ CHR² O)_(n) R³ will be ##STR11##

It is thus apparent that there are two preferred processes for preparingpolymers according to the invention.

The first process (a) comprises polymerising (usually by free-radicalinitiation) an olefinically unsaturated carboxylic acid (or anesterifiable or amidifiable derivative thereof) and partiallyesterifying or amidifying the resulting polyacid (or derivative thereof)with at least one alcohol of formula HO(CHR¹ CHR² O)_(n) R³ or at leastone amine of formula H₂ N(CHR¹ CHR² O)_(n) R₃.

The second (and generally more preferred) process (b) comprisescopolymerising (usually by free-radical initiation) at least onepolymerisable ester or amide, formed from the reaction of a firstolefinically unsaturated carboxylic acid (or an esterifiable oramidifiable derivative thereof) and an alcohol of formula HO--CHR¹ CHR²O)_(n) R³ or an amine of formula H₂ N--CHR¹ CHR² O)_(n) R³, with atleast one second olefinically unsaturated carboxylic acid.

Both processes will yield repeat units of structure A and structure B ashereinbefore defined.

In the polymers of the invention, it is preferable that substantiallyall the R¹ and R² groups are hydrogen so that (CHR¹ CHR² O)_(n) is (CH₂CH₂ O)_(n). Such groups may be derived from the alcohol HO--(CH₂ CH₂O)_(n) R³ or the corresponding amine H₂ N--CH₂ CH₂ O)_(n) R³. Where aproportion of the R¹ and R² groups in the polymer are methyl, all the R¹or R² groups in one or more of the (CHR¹ CHR² O)_(n) chains may bemethyl or one or more (but not all) of the R¹ or R² groups in one ormore of the (CHR¹ CHR² O)_(n) chains may be methyl. R¹ and R² cannot,however, both be methyl in the same unit (CHR¹ CHR² O) as specifiedhereinbefore. Such a chain could for example be derived from an aminesuch as H₂ N--CH(CH₃)CH₂ O)₂ (CH₂ CH₂ O)₄ C₄ H₉ (where CHR¹ CHR² O isCH(CH₃)CH₂ O and CH₂ CH₂ O, n is 6, and C₄ H₉ is normal butyl), or otheranalogous amines (varying CHR¹ CHR² O and n). It could also be derivedfrom an alcohol, such as HOCH(CH₃)CH₂ OH.

Preferably R³ is a lower alkyl group containing up to 5 carbon atoms,e.g. n-butyl or (more preferably) methyl. It may, nevertheless, behydrogen.

Specific examples of polymers that we have prepared and investigatedhave repeating units structures A and B as follows:

    __________________________________________________________________________    A            B                                                                __________________________________________________________________________     ##STR12##                                                                                  ##STR13##                                                        ##STR14##                                                                                  ##STR15##                                                        ##STR16##                                                                                  ##STR17##                                                        ##STR18##                                                                                  ##STR19##                                                        ##STR20##                                                                                  ##STR21##                                                        ##STR22##                                                                                  ##STR23##                                                        ##STR24##                                                                                  ##STR25##                                                        ##STR26##                                                                                  ##STR27##                                                       __________________________________________________________________________

In the polymers of the invention, n is a number of from 1 to 60 asdefined herein. Often, however, n is preferably from 1 to 20. It shouldbe appreciated that most polymers according to the invention(particularly those made with precursors providing the alkyleneoxygrouping that have been obtained commercially) may have a small spreadof alkyleneoxy chain length so that n may represent an average value insuch cases.

As defined herein, the ratio of --CO₂ H groups to --CHR¹ CHR² O-- groupsis within the range of from 1:20 to 20:1. Preferably the ratio is from1:5 to 5:1.

Typically the polymers of the invention have weight average molecularweights within the range of from 5000 to 500,000, although we do notexclude the possibility that suitable polymers having molecular weightsoutside this range may be used in the present invention.

The groups X and Y may be unsubstituted hydrocarbyl radicals or may besubstituted with groups such as hydroxy, alkoxy and halogen (chlorine)provided the desired properties of the polymers are not adverselyaffected. Preferably however, the groups X and Y are unsubstituted, i.e.have only groups linked L and M attached to them.

The polymers of the invention may also contain up to 50% w/w (i.e. 0 to50% w/w), sometimes up to 10% w/w (i.e. 0 to 10% w/w), of repeatingunits other than those of structures A and B, which form the backbonethereof, and these may provide one or more in-chain or pendant heteroatoms (per unit). Such other repeating units must not of courseadversely affect the properties of the resulting oral hygienecompositions. More usually however, the polymers of the invention havesubstantially all their repeating units with structures A and B.

The oral hygiene compositions of the invention generally have said atleast one polymer present therein at a concentration of about 0.05 to 30weight % of the composition, the preferred concentration range beingfrom about 0.1 to 5 weight % (and more preferably 0.2 to 2 weight %).

While the oral hygiene compositions of the invention will usually haveonly one polymer according to the invention (as defined hereinbefore)therein, it is quite feasible to use two or more such polymers in thecompositions.

Suitable conventional pharmaceutically acceptable vehicles that can beemployed in the oral hygiene compositions of the present inventioninclude water, ethanol (wherein water, or a water/ethanol mixture willoften be a major component of the vehicle); such humectants aspolypropylene glycol, glycerol and sorbitol; such gelling agents ascellulose derivatives, for example, Methocel, carboxymethylcellulose(CMC 7MF) and Klucel HF, polyoxypropylene/polyoxyethylene blockcopolymers, for example, Pluronic F-127, Pluronic F-108, Pluronic P-103,Pluronic P-104, Pluronic P-105, and Pluronic P-123, colloidial magnesiumaluminosilicate complexes such as Veegum, and mucoprotein thickeningagents such as Carbopol 934; gel stabilisers such as the silicondioxides, for example, Cab-O-Sil M5, and polyvinylpyrrolidone;sweeteners such as sodium saccharin; preservatives such as citric acid,sodium benzoate, cetylpyridinium chloride, potassium sorbate, methyl andethyl parabens; surfactants such as sodium lauryl sulfate, sodiumcocomonoglymeride sulfonate, sodium lauryl sarcosinate andpolyoxyethylene isohexadecyl ether (Arlasolve 200) and approved coloursand flavours.

The oral hygiene compositions of the invention may be in the form of anyconventional pharmaceutically acceptable oral hygiene formulation thatcontains (and is compatible with) an effective amount of a polymer asdefined herein. Such formulations include, for example, mouthwashes,rinses, irrigating solutions, abrasive and nonabrasive gel dentifrices,denture cleansers, coated dental floss, coated or impregnated toothbrushbristle (natural or synthetic), and interdental stimulator coatings,chewing gums, lozenges, breath fresheners, foams and sprays.

The present invention is now illustrated by the following examples. Theprefix C for a number denotes a comparative example.

Examples 1 to 17, and C18 to C23

Examples 1 to 17 illustrate polymers (and their preparation) accordingto the present invention of which polymers oral hygiene compositionsaccording to the invention may be comprised. It was found thatcomonomers providing units A and B reacted so as to give polymers inwhich the mole ratio of A to B units therein was close to the mole ratioused for the starting monomers (indicating approximately equalreactivities), so that the latter ratio could be used for calculatingthe former, which was also checked in most cases using ordinaryanalytical techniques (chemical analysis, NMR, and acid-basetitrations).

A typical polymer preparation, specifically applicable to the polymersof Examples 1 to 6, 9, 10, and 12 is now described. (Dry chemicals andsolvents were used.)

Methacryloyl chloride (0.11 moles) was added slowly with stirring to aslight molar excess of a 30% solution of 2,6-lutidine in toluene. Fumingoccurred and a white precipitate formed. The mixture was cooled in anice-bath and methoxy-ended polyethylene glycol (0.10 moles) was addeddropwise over 3 hours with stirring under nitrogen. A copious whiteprecipitate formed and stirring was continued for a further 2 hours. Thereaction mixture was allowed to warm to room temperature. Theprecipitate was filtered off and washed with small volumes of toluene.The combined filtrates were evaporated to dryness (over 90% yield) on arotary evaporator at 45° C. The structure of the product was confirmed,by IR, NMR and vinyl bond titration, as substantiallyα-methoxy-ω-methacryloyloxy-polyethylene glycol.

The monomers methacrylic acid andα-methoxy-ω-methacryloyloxy-polyethylene glycol, in selected molarratios (total 25 grams), and solvent (usually ethanol or ethanol/watermixture) (300 ml) were charged to a reaction vessel at 70° C. Initiator(1.8×10⁻³ moles) in solvent (20 mls) was added and the reaction mixturewas stirred (200 rpm) at 70° C. for 24 hours. Further (initiator (7×10⁻⁴moles) in solvent (20 ml) was added and the reaction was continued for afurther 24 hours. The reaction mixture was evaporated on a rotaryevaporator under reduced pressure to leave a copolymer (usually about95% yield). The compositions of the copolymers are given in Table 1,which also gives the values for n and the ratio of (CO₂ H) to (CHR¹ CHR²O) groups.

Substantially the same sort of technique was employed for thepreparation of the polymers of Examples 7, 8, 11, 13, 14, 16 and 17except that:

for the preparation of the polymer of Example 7, acrylic acid was usedin place of methacrylic acid for the polymerization

for the preparation of the polymer of Example 8, N-methacryloyl alanine,i.e. CH₂ =CH(CH₃)CONH(CH₃)CO₂ H, prepared by reacting the Na salt ofalanine with methacryloyl chloride, was used in place of methacrylicacid for the polymerization

for the preparation of the polymer of Example 14, N-acryloyl hydroxyglycine, i.e. CH₂ =CHCONHCH(OH)CO₂ H, was used in place of methacrylicacid for the polymerization

for the preparation of the polymers of Examples 13 and 17, there wasused, respectively, hydroxyethyl methacrylate and hydroxypropylmethacrylate in place of α-methoxy-ω-methacryloyl-polyethylene glycol.

for the preparation of the polymer of Example 11, the N-methacryloylderivate of C₄ H₉ (OCH₂ CH₂)₄ (OCH₂ CH(CH₃))₂ NH₂, i.e. CH₂=CH(CH₃)CONH(CH(CH₃)CH₂ O)₂ (CH₂ CH₂ O)₄ C₄ H₉ was used in place ofα-methoxyω-methacryoyloxy-polyethylene. This monomer was made byreacting the amino compound with methacryloyl chloride in toluene assolvent and in the presence of 2,6-dimethyl pyridine as acid acceptor

for the preparation of the polymer of Example 16, the polymerization wasphoto initiated at room temperature using benzoin methyl ether.

The compositions of these polymers are also given in Table 1.

The polymer of Example 15 was prepared by the alternative technique ofpartially esterifying or amidifying an already-polymerised carboxy acidor derivative thereof. A maleic anhydride/methyl vinyl ether copolymer(1/1 molar) of medium molecular weight (Aldrich) was reacted at anelevated temperature with the calculated amount of C₄ H₉ (OCH₂ CH₂)₄(OCH₂ CH(CH₃))₂ NH₂ (available commercially), under anhydrous conditionsto provide a partially amidified product (each anhydride group reactingwith the amine forming adjacent carboxyl and amido groups). This productwas then heated with water (excess) to hydrolyse the residual unreactedanhydride groups to form adjacent carboxyl groups. This yielded,respectively, the repeating units ##STR28## so that the repeat units ofstructures A and B were respectively ##STR29##

The composition of this polymer is also given in Table 1.

The polymers of C18 to C21 were prepared for comparative purposes, usingsubstantially the same technique as used for Examples 1 to 6, etc,except that:

for the preparation of the polymers of Examples C18, C19 and C20 themonomers for the polymerisations also included methyl methacrylate (MMA)which therefore became incorporated into the polymer backbone. The molarratio of MA:MMA used in these three examples was 10:1

for the preparation of the polymer of Example C21, the MA monomer wasreplaced entirely by MMA, so that the polymer contained no acidic Aunits

The compositional details of these comparative polymers is also given inTable 1.

The weight average molecular weights of most of the polymers weredetermined (using gel permeation chromatography with polystyrene orpolyethylene oxide standards, and dimethyl formamide or tetrahydrofuranas solvent) and were mostly within the range 5000 and 500,000.

The product of Example 8 of U.S. Pat. No. 3,542,917 was also preparedfor comparative purposes, being denoted by Example C22. Example C23denotes an analogous product to that of Example 8 of U.S. Pat. No.3,542,917 but using polyethylene glycol in place of polypropyleneglycol.

                                      TABLE 1                                     __________________________________________________________________________                                 Ratio of                                                                  Molar                                                                             (CO.sub.2 H):                                                             Ratio                                                                             (CHR.sup.1 CHR.sup.2 O)                          Ex. Repeating Unit                                                                             Other                                                                             Value                                                                             of  groups                                           No. Type A                                                                             Type B  Units                                                                             of n                                                                              A:B (approx.)                                        __________________________________________________________________________    1   MA   PEG350MAt                                                                             --  8   3:1 1:2.7                                            2   MA   PEG2000MAt                                                                            --  45  3:1 1:15                                             3   MA   PEG2000MAt                                                                            --  45  10:1                                                                              1.4.5                                            4   MA   PEG150MAt                                                                             --  3   3:1 1:1                                              5   MA   PEG350MAt                                                                             --  8   6:1 1:1.3                                            6   MA   PEG1000MAt                                                                            --  23  3:1 1:7.7                                            7   AA   PEG350MAt                                                                             --  8   3:1 1:2.7                                            8   MAtAl                                                                              PEG350MAt                                                                             --  8   3:1 1:2.7                                            9   MA   PEG350MAt                                                                             --  8   10:1                                                                              1.25:1                                           10  MA   PEG350MAt                                                                             --  8   3.5:1                                                                             1:2.3                                            11  MA   JMAt    --  6   6:1 1.1:1                                            12  MA   PEG1000MAt                                                                            --  23  25:1                                                                              1:1                                              13  MA   HEMAt   --  1   1:1 1:1                                              14  NG   PEG350MAt                                                                             --  8   6:1 1:1.3                                            15  Mal  MalJ    MEV 6   7:1 1.17:1                                           16  MA   PEG350MAt                                                                             --  8   6:1 1:1.3                                            17  MA   HPMAt   --  1   1:1 1:1                                              C18 MA   PEG550MAt                                                                             MMA 12  1:2.75                                                                            1:33                                             C19 MA   PEG2000MAt                                                                            MMA 45  1:2 1:90                                             C20 MA   PEG350MAt                                                                             MMA 8   1:2.75                                                                            1:22                                             C21 --   PEG350MAt                                                                             MMA 8   no A                                                                              no A                                             C22 As for Ex 8 of US 3542917                                                 C23 As for Ex 8 of US 3542917 but using PEG instead of PPG                    __________________________________________________________________________    Abbreviations in Table 1                                                      MA:     unites derived from methacrylic acid.                                 PEG350MAt:                                                                            units derived from polyethylene glycol                                        (PEG) capped with a methoxy and a                                             methacryloyl group, i.e. from                                                 CH.sub.2C(CH.sub.2)COO(CH.sub.2 CH.sub.2 O).sub.n CH.sub.3                    where the molecular wt of the polyethylene                                    glycol PEG) portion thereof is 350.                                   PEG2000MAt:                                                                           as PEG350MAt but with PEG portion                                             molecular wt of 2000.                                                 PEG150MAt:                                                                            as PEG350MAt but with PEG portion                                             molecular wt of 150.                                                  PEG1000MAt:                                                                           as PEG350MAt but with PEG portion                                             molecular wt of 1000.                                                 PEG550MAt:                                                                            as PEG350MAt but with PEG portion                                             molecular wt of 550.                                                  AA:     units derived from acrylic acid.                                      MAtAl:  units derived from N-methacryloyl alanine,                                    i.e. from                                                                     CH.sub.2CH(CH.sub.3)CONHCH(CH.sub.3)CO.sub.2 H                        JMAt:   units derived from amide formed between                                       methacrylic acid and the amine of formula                                     NH.sub.2 (CH(CH.sub.3)CH.sub.2 O).sub.2 (CH.sub.2 CH.sub.2                    O).sub.4 C.sub.4 H.sub.9, i.e.                                                from                                                                          CH.sub.2CH(CH.sub.3)CONH(CH(CH.sub.3)CH.sub.2 O).sub.2 (CH.sub.2              CH.sub.2 O).sub.4 C.sub.4 H.sub.9                                             where C.sub.4 H.sub.9 is normal butyl.                                Mal:                                                                                   ##STR30##                                                            MalJ:   units of formula                                                               ##STR31##                                                            MEV:    units derived form methyl vinyl ether.                                MMA:    units derived from methyl methacrylate.                               HEMAt:  units derived form hydroxyethyl                                               methacrylate.                                                         HPMAt:  units derived from hydroxypropyl                                              methacrylate.                                                         NG:     units derived form N-acryloyl hydroxy glycine.                        PPG:    polypropylene glycol.                                             

These examples illustrate the extent of the reduction in bacterialadhesion obtained with use of the polymers hereinbefore defined.

Polished hydroxyapatite discs (25 mm diameter) were used as a modeltooth surface. S. mutans NCTC 10449 was used as the standard organism.

The discs were used clean or were Pellicle-coated by incubating infreshly collected whole saliva (from a single donor) for 1 hour at 37°C., followed by brushing with water 5 times.

The aforementioned discs were held in a 1% w/v aqueous (or alcoholic)solution of the polymers in a petri-dish for 5 minutes at ambienttemperature and were then washed by shaking 5 times in a container offlowing water ("treated discs").

S. mutans NCTC 10449 were grown at 37° C. in a Brain/Heart Infusiongrowth medium. A portion (20 mls) of the culture at a concentration of10⁹ cells/ml was centrifuged at 4,000 rpm for 10 minutes and the cellswere resuspended in modified Ringer's salts solution (0.54 grams perliter NaCl; 0.02 grams per liter KCl; 0.03 grams per liter CaCl₂ ; and0.75 grams per liter sodium mercaptoacetate), recentrifuged, resuspendedand diluted 10x in Ringer's salts solution.

The treated discs were immersed in the aforementioned suspension for 2hours. The treated discs were then washed by shaking 5 times in acontainer of flowing water and bacteria adhering thereto were stainedusing Loeffler's Methylene Blue (30 ml of 95% ethanol, 0.3 grammethylene blue and 100 ml of water). Microscopic examination was used toestimate the reduction in bacterial adhesion of the clean discs andpellicle-coated discs versus untreated control discs. The results forthe clean discs are given in Table 2.

                  TABLE 2                                                         ______________________________________                                                  Polymer                                                             Example   from     % Reduction.sup.a compared with                            No.       Ex. No.  untreated control discs                                    ______________________________________                                        24        1        96                                                         25        2        74                                                         26        3        92                                                         27        4        97                                                         28        5        98                                                         29        6        93                                                         30        7        91                                                         31        8        90                                                         32        9        95                                                         33        10       95                                                         34        11       97                                                         35        12       96                                                         36        13       98                                                         37        14       99                                                         38        15       99                                                         39        16       99                                                         40        17       99                                                         C41       C18      25                                                         C42       C19      +17                                                        C43       C20      +18                                                        C44       C21       0                                                         C45       C22      15                                                         C46       C23      +41                                                        ______________________________________                                         .sup.a average of several discs                                               +denotes an increase in adhesion rather than a reduction                 

In the case of pellicle-coated discs, the results of extensive testingusing selected polymers, viz those of Examples 1, 5, and 6, were 90%,97% and 87% reduction respectively.

EXAMPLES 47 AND 48

Examples 24 and 28 were repeated using extracted human teeth which hadbeen brushed. Similar results were obtained.

EXAMPLES 49 AND 54

The polymer of Example 5 was tested for its effectiveness in preventingthe adherent deposition of a range of oral bacteria other than S. mutansNCTC 10449, the evaluation procedure being otherwise the same as inExamples 24 to 40, C41 to C46 (clean discs only). The results are givenin Table 3.

                  TABLE 3                                                         ______________________________________                                        Example                % Reduction compared with                              No.    Bacteria        untreated control discs                                ______________________________________                                        49     S. sanguis 11085                                                                              96                                                     50     S. salivarious 11389                                                                          99                                                     51     Streptococcus Group H1                                                                        99                                                     52     Streptococcus Group H2                                                                        99                                                     53     Saliva Isolate A                                                                              98                                                     54     Saliva Isolate B                                                                              99                                                     ______________________________________                                    

EXAMPLES 55 TO 68, AND C69

A number of polymers according to the invention, identified as beingextremely promising by the petri-dish experiments described in thepreceding examples, were subjected to a more severe challenge usingflowing conditions in order to more closely simulate the environmentinside a mammalian (human) mouth. A "Drip-Machine" was developed forthis purpose, and consisted of a glass reservoir containingapproximately 400 ml of a stirred solution of S. mutans (prepared as forthe petri-dish experiments). An 8 channel peristaltic pump was usedcontinuously to drip (using syringe needles) 8 flows of the bacterialsuspension over 8 samples (clean hydroxyapatite discs treated with 1%aqueous (or alcoholic) solution of polymer, or untreated, as before)suspended on a mesh above the reservoir, the bacterial suspension thusbeing recycled. The tests were carried out in an incubating oven at 37°C. and experiments were routinely run overnight (about 17-19 hours).After the adhesion stage, the substrates were washed, stained andexamined, as in the petri-dish experiments described above. Acomposition containing the polymer of Example C22 was also tested forcomparison purposes. The results are shown in Table 4.

                  TABLE 4                                                         ______________________________________                                                  Polymer                                                             Example   from     % Reduction compared with                                  No.       Ex. No.  untreated control discs                                    ______________________________________                                        55         1       64                                                         56         3       68                                                         57         4       88                                                         58         5       94                                                         59         6       63                                                         60         7       91                                                         61         8       60                                                         62        11       90                                                         63        12       98                                                         64        13       36                                                         65        14       99                                                         66        15       95                                                         67        16       99                                                         68        17       99                                                         C69       C22      +25                                                        ______________________________________                                         +denotes an increase in adhesion rather than a reduction.                

It can be seen that all the polymer compositions according to theinvention used is Examples 55 to 68 gave a positive degree of utilityfor preventing adherent bacterial deposition under the more severetesting conditions employed in the "Drip-Machine", and those containingthe polymers of Example 5, 7, 11, 12, 14, 15, 16, and 17 wereparticularly noteworthy by giving % reductions of 90 or above even underthese more sever conditions.

We claim:
 1. Process for preventing or inhibiting the adherentdeposition of cariogenic or other oral bacteria and plaque formedtherefrom on teeth, which process comprises applying to the teeth anoral hygiene composition comprising an effective among of at least onepolymer has a molecular weight of at least about 5000 and units ofgeneral structure A ##STR32## and one or more repeating units of generalstructure B ##STR33## wherein X, which in the repeating units ofstructure A may be the same or different, and Y, which is the repeatingunits of structure B may be the same or different, are unsubstitutedhydrocarbyl residues or residues substituted with groups such ashydroxy, alkoxy and halogen provided that the desired properties of thepolymer are not adversely effected by such substituents, said residuesproviding a backbone for the polymer;R¹, which in the same repeatingunit of structure B (when n or q is 2 or more) or in different repeatingunits of structure B may be the same or different, is hydrogen ormethyl; R², which in the same repeating unit of structure B (when n or qis 2 or more) or in different repeating units of structure B may be thesame or different, is hydrogen or methyl; except that R¹ and R² in asingle unit (CHR¹ CHR² O) cannot both be methyl; R³, which in the samerepeating unit of structure B (when q is 2 or more) or in differentrepeating units of structure B may be the same or different, ishydrogen, or a lower alkyl group containing up to 5 carbon atoms, or anacyl groups derived from an alkanoic acid having up to 5 carbon atoms; nis a number of from 1 to 60; p is a number of from 1 to 4, and q is anumber of from 1 to 4; and wherein each (CH₂ H) group is joined via anintermediary or intermediaries L to the hydrocarbon residue X, and incases where p is 2 to 4 may be joined by 1 to the same or differentcarbon atoms of x; and wherein L represents one or more intermediaries,and wherein L may be the same or different in the repeating units ofstructure A and is selected from one or more direct links and one ormore groups of atoms each group providing a chain of one or more atomsfor linking a (Co₂ H) group with X, except that more than two (CO₂ H)groups cannot be directly linked to the same carbon atom in X; andwherein each (CHR¹ CHR² O)_(n) group is joined via an intermediary orintermediaries M to the hydrocarbyl residue Y, and in cases where q is 2to 4 may be joined to the same or different carbon atoms of Y; andwherein M represents one or more intermediaries, and wherein M may bethe same ox different in the repeating units of structure B and isselected from one or more direct links and one or more groups of atomseach group providing a chain of one or more atoms for lining a (CHR¹CHR² O)_(n) group with Y, except that more than two (CHR¹ CHR² O) groupscannot be directly linked to the same carbon atom in Y; and wherein theratio of the member of --CO₂ H groups to the number of --CHR¹ CHR² O--groups is within the range of from 1:20 to 20:1; and said compositionalso comprising a pharmaceutically acceptable vehicle for said polymer.2. A process according to claim 1 wherein said process is presenttherein at a concentration of 0.05 to 30 weight % of the composition. 3.A process according to claim 1 in the form of a mouthwash, rinse,irrigating solution, abrasive or nonabrasive gel dentifrice, denturecleaner, coated dental floss, toothbrush bristle coating or impregnant,interdental stimulator coating, chewing gum, lozenge, breath freshener,foam or spray.
 4. A process according to claim 1 wherein L is selectedfrom one or more direct links and one or more groups of atoms eachproviding a chain of one or more carbon and/or hetero atoms.
 5. Aprocess according to claim 1 wherein m is selected from one or moregroups of atoms each group providing a chain of one or more carbonand/or hetero atoms.
 6. A process according to claim 5 wherein M isselected from one or more --COO-- and --CONH-- groups.
 7. A processaccording to claim 1 wherein p in structure A is 1 or
 2. 8. A processaccording to claim 1 wherein q in structure B is 1 or
 2. 9. A processaccording to claim 1 wherein structure A is the repeat unit derived fromthe polymerization of a polymerizable olefinically unsaturatedcarboxylic acid.
 10. A process according to claim 9 wherein said acid isacrylic acid, methacrylic acid, maleic or fumaric acid, N-methacryloylalanine, or U-acryloyl hydroxy glycine, whereby the correspondingstructures A are respectively: ##STR34##
 11. A process according toclaim 1 wherein structure B is the repeating unit derived from thepolymerization of a polymerizable olefinically unsaturated ester oramide formed from an olefinically unsaturated carboxylic acid (or anesterifiable or amidifiable derivative thereof) and a hydroxy compoundof formula HO--CHR¹ CHR² O)_(n) R³ (to form the ester) or an amine offormula H₂ N--(CHR¹ CHR² O)_(n) R³ (to form the amide).
 12. A processaccording to claim 11 wherein the acid used for the ester or amideformation is methacrylic acid, and the corresponding structure B arerespectively: ##STR35##
 13. A process according to claim 1 wherein bothstructures A and B are the repeat units resulting from the partialesterification or amidification of an already-polymerized olefinicallyunsaturated carboxylic acid (or an esterifiable or amidifiablederivative thereof) using an alcohol of formula HO--(CHR¹ CHR² O)_(n) R³or an amide of formula H₂ N--(CHR¹ CHR₂ O)_(n) R³.
 14. A processaccording to claim 13 wherein already-polymerised acid or acidderivative is the polymerized acid anhydride of maleic acid, or repeatunit ##STR36## and the resulting repeating units A and B afteresterification or amidification comprising respectively ##STR37##
 15. Aprocess according to claim 1 wherein substantially all the R¹ and R²groups are hydrogen so that (CHR¹ CHR¹ O)_(n) is (CH₂ CH₂ O)_(n).
 16. Aprocess according to claim 1 wherein one or more of, or all of, the R¹groups or one or more of, or all of, the R² groups in one more of the(CHR¹ CHR² O)_(n) chains are methyl.
 17. Process for preventing orinhibiting the adherent deposition of cariogenic or other oral bacterialand plaque formed therefrom on teeth, which process comprises applyingto the teeth an effective amount of a composition comprising at leastone polymer and a pharmaceutically acceptable vehicle for said polymer,which polymer has a molecular weight of at least about 5000 andcomprises repeating units of structure A and repeating units ofstructure B, wherein said polymer comprises one of the following pairsof structures for A and B:

    __________________________________________________________________________    A             B                                                               __________________________________________________________________________     ##STR38##                                                                                   ##STR39##                                                       ##STR40##                                                                                   ##STR41##                                                       ##STR42##                                                                                   ##STR43##                                                       ##STR44##                                                                                   ##STR45##                                                       ##STR46##                                                                                   ##STR47##                                                       ##STR48##                                                                                   ##STR49##                                                       ##STR50##                                                                                   ##STR51##                                                       ##STR52##                                                                                   ##STR53##                                                      __________________________________________________________________________      wherein the ratio of --CO.sub.2 H groups to --CHR.sup.1 CH.sub.2 O--     groups (where R.sup.1 is H or methyl as depicted above) is from 1:20 to     20:1.


18. A process according to either of claims 1 and 17 wherein saidpolymer has a weight average molecular weight within the range of from5000 to 500,000.
 19. A process according to either of claims 1 and 17wherein the backbone of said polymer is derived from said repeatingunits A and said remaining units B and 0 to 50% w/w of at least oneother repeating unit structure which does not adversely affect theproperties of the oral hygiene composition.